Role of dopamine in the regulation of endothelial cell functions in diabetes

多巴胺在糖尿病内皮细胞功能调节中的作用

基本信息

批准号：
8460332
负责人：
Sujit Basu
金额：
$ 33.17万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-15 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8460332
关键词：
Adult Agonist Amputation Animals Apoptosis Atherosclerosis Blood Circulation Blood Glucose Blood Vessels Blood flow Bone Marrow Bone Marrow Transplantation Caring Cell Proliferation Cell physiology Cells Centers for Disease Control and Prevention (U.S.)Cutaneous Cyclic AMP-Dependent Protein Kinases Data Defect Dermal Diabetes Mellitus Diabetic mouse Diabetic wound Disease Dopamine Dopamine D1 Receptor Dopamine Receptor Doppler Echocardiography Electron Spin Resonance Spectroscopy Endothelial Cells Experimental Designs Functional disorder Glucose Goals Growth Factor Healed Homing Human Immunohistochemistry Impaired wound healing Knowledge Lasers Lead Life Mediating Modeling Monitor Mus NADPH Oxidase Neurotransmitters Oxidases PECAM1 gene Pathway interactions Peripheral Play Process Production Reactive Oxygen Species Refractory Regulation Reporting Role Simulate Skin Source Stem cells Streptozocin Stromal Cell-Derived Factor 1 Stromal Cells Tissues Tube Up-Regulation Vascular Diseases Wound Healing cytokine density design digital imaging disorder prevention effective therapy healing macrophage neovascularization novel receptor repaired research study tissue culture vascular bed wound

项目摘要

DESCRIPTION (provided by applicant): In diabetes mellitus, dysfunctional endothelial cells (EC) and low numbers of endothelial progenitor cells (EPC) in the peripheral circulation lead to several vascular disorders like impaired wound healing. Recent reports indicate reactive oxygen species (ROS) and low expression of the cytokine, stromal cell-derived factor-1¿ (SDF-1¿) to be important causes of these pathological conditions. As neurotransmitter dopamine (DA) is reported to regulate ROS production and because DA may also control SDF-1¿ synthesis, we therefore hypothesized that DA could normalize EC functions and SDF-1¿ expression in diabetic wound tissues. Aim 1 will investigate the effect of DA D1 receptors on ROS induced EC functions. In Aim 2, the role of DA D1 receptors on SDF-1¿ production by macrophages will be determined and finally Aim 3 will examine the effects of DA D1 receptors on ROS production and neovascularization in diabetic wound tissues. PUBLIC HEALTH RELEVANCE: Endothelial cell dysfunctions and significantly decreased production of growth factors and cytokines in diabetes mellitus lead to several vascular disorders like impaired wound repair and healing. According to the Center for Disease Control and Prevention, refractory diabetic wounds lead to over 72,000 amputations each year despite of advances in wound care, therefore the goal of this application is to develop dopamine mediated newer and an effective therapy for this pathological condition.

描述（由申请人提供）：在糖尿病中，外周循环中功能失调的内皮细胞（EC）和内皮祖细胞（EPC）数量减少会导致多种血管疾病，例如伤口愈合受损。最近的报告表明活性氧（ROS）。以及细胞因子、基质细胞衍生因子-1 的低表达(SDF-1¿) 是这些病理状况的重要原因，因为据报道神经递质多巴胺 (DA) 可以调节 ROS 的产生，并且 DA 也可能控制 SDF-1¿因此，我们探索了 DA 可以使 EC 功能和 SDF-1 正常化。目标 1 将研究 DA D1 受体对 ROS 诱导的 EC 功能的影响。目标 2 将研究 DA D1 受体对 SDF-1 的作用。将确定巨噬细胞的产生，最后目标 3 将检查 DA D1 受体对糖尿病伤口组织中 ROS 产生和新血管形成的影响。公众健康相关性：根据疾病控制和预防中心的数据，糖尿病患者的内皮细胞功能障碍以及生长因子和细胞因子的产生显着减少会导致多种血管疾病，例如伤口修复和愈合受损，难治性糖尿病伤口导致超过 72,000 例截肢。尽管伤口护理多年来取得了进步，因此该应用的目标是开发多巴胺介导的针对这种病理状况的更新且有效的疗法。